Summary: 4-channel multimodal ultrathin-flexible SFE for cancer diagnosis and therapy Minimally-invasive optical imaging is being advanced by molecular probes that enhance contrast using fluorescence. The applications in cancer imaging are very broad, ranging from early diagnosis of cancer to the guiding of interventions, such as surgery. The high-sensitivity afforded by wide-field fluorescence imaging using scanning laser light is being developed for these broad applications. The platform technology is the SFE (Scanning Fiber Endoscope), which places a sub-mm scanner at the tip of a highly flexible scope. Because several different laser wavelengths can be mixed and scanned together, full-color reflectance imaging can be combined with fluorescence imaging in a 4-channel multimodal SFE. The goal of this project is to develop the first prototype VerAvanti 4-channel multimodal SFE (mmSFE) for cancer imaging applications. VerAvanti is a start-up medical device company located in Redmond, WA, founded and staffed with engineering graduates from the University of Washington (UW), where the SFE was invented and tested in pilot clinical trials. VerAvanti has exclusive license to commercialize the SFE technology for medical imaging and a 3-channel full color SFE (using red, green, and blue reflectance) is already in pilot manufacturing and testing. This project will rapidly translate the mmSFE technology from its origins at UW into a working prototype by adding near infrared (NIR) fluorescence as the 4th imaging channel. Importantly the VerAvanti mmSFE will be designed for efficient manufacturing in a modular format with reduced part numbers. This will allow two very different cancer imaging applications to be commercially available for upcoming clinical trials that rely on molecular imaging of cancer. The first application is fluorescence image-guided surgery, specifically brain tumors that are labeled with BLZ- 100, a peptide probe with a NIR dye to highlight cancer cells, especially at the margin with healthy brain tissue. The ultrathin and flexible mmSFE will allow less invasive surgeries and allow the guided tool to avoid the most important areas to be left intact. VerAvanti will design and develop the prototype to specified benchmarks which will be tested at UW using realistic phantoms and feedback from clinicians. The challenge for VerAvanti is extending from 3 to 4 laser wavelengths across the visible to NIR with a clinical interface that neurosurgeons prefer. The second application is providing 3 fluorescence imaging channels concurrently with grayscale reflectance imaging for the purpose of making an accurate cancer diagnosis in the pancreatobiliary ducts that are often too small to obtain sufficient biopsy tissue. Feasibility of the modular mmSFE design using 1 to 3 fluorescence imaging channels (and reflectance for situational awareness) in a 1.5-mm diameter flexible scope will be determined, but only the mmSFE for the first application will be prototyped and neurosurgeon tested.